Gene and Point Mutations 



201 



radiations produce a mutational spectrum 

 much like the spontaneous one, as would 

 seem reasonable from the fact that the radi- 

 ant energy involved is more or less randomly 

 distributed in the nucleus and generally en- 

 hances chemical reactions of all kinds. How- 

 ever, the point mutational spectrum is some- 

 what different for different chemicals, and is 

 different from that for natural or radiation 

 mutation agents. This can be attributed to 

 either the nonrandom penetration of these 

 chemical substances into the nucleus, or 

 the specific capacities that these have of com- 

 bining with different nuclear chemicals, or 

 both. Nevertheless, the frequency of point 

 mutations, which increases linearly with the 

 dose of ionizing radiation (although the rate 

 is influenced by the amount of oxygen 

 present), probably also increases linearly 

 with the nuclear dose of many different 

 chemical mutagens. So point mutations 

 show no threshold dose with these mu- 

 tagens, and the number of point mutations 

 produced by a given total dose is constant, 

 regardless of the rate of delivery. However, 

 in the case of ultraviolet light, which is not a 

 highly energetic radiation, the situation is 

 otherwise. Here the individual quantum of 

 energy has a probabiUty of inducing point 

 mutation which is considerably less than 

 100 per cent. This means that several quanta 

 can cooperate to produce mutation, so that 

 the point mutation rate increases faster than 

 linearly with dose, at least at low doses, and 

 an attenuated dose is less mutagenic than a 

 concentrated one. 



Point mutation is not restricted to the 

 genes of any particular kind of cell. It oc- 

 curs in males and females, in somatic tissues 

 of all kinds, and in the diploid and haploid 

 cells of the germ line. It has been found that 

 perifertilization stages (later stages in game- 

 togenesis and very early developmental 

 stages) are relatively rich in spontaneous 

 point mutations. It is not surprising that 

 despite the very great differences in life span, 



there is not a greater difference in sponta- 

 neous mutation rate between flies, mice, and 

 men. For, if most germ line mutations occur 

 in the perifertilization stages, these rates 

 would be quite similar, since these different 

 organisms are not very different in the length 

 of time occupied by these stages. A further 

 similarity exists among these species, in that 

 there is not a very great difference in the num- 

 ber of cell divisions required to go from a 

 gamete of one generation to a gamete of the 

 next. In fact, the differences in mutation rate 

 for these organisms are approximately pro- 

 portional to the differences in the number of 

 germ cell divisions per generation. 



This brings to mind the following ques- 

 tions: When, during the history of the gene, 

 does the event of mutation occur? Can the 

 old gene itself undergo mutation whether it 

 is or is not in the process of synthesizing a 

 new one? Can "mutations" occur during the 

 course of synthesis of what is to be the new 

 gene? The fact already mentioned, that 

 point mutation rates in Drosop/iila, mouse, 

 and man are proportional to the numbers of 

 cell divisions that occur, suggests that some of 

 these mutations occur at the time of synthesis 

 of the new gene, although this does not 

 specify whether it is the old or the new gene 

 that becomes mutant. It has been found that 

 the aging of spermatids and sperm of Dro- 

 sophila increases their point mutation rate. 

 Since these nondividing cells do not have 

 their viability impaired when they are 

 aneuploid, the increase in point mutations 

 may be due to an effect upon the old gene, 

 which is physiologically quiescent and prob- 

 ably not actively synthesizing new genes. 

 The occurrence of mutation in the old gene 

 would mean that point mutational changes 

 can occur while a gene is linearly attached to 

 its genie neighbors. However, the higher 

 mutation rate observed after cells are aged 

 may also be explained as resulting from the 

 accumulation, with time, of a mutagen which 

 acts on the old or new gene once gene repli- 



